JOURNAL
OF SURGICAL
RESEARCH
48,313-318
(1990)
Portal Hypertension Predisposes the Gastric Mucosa to Hemorrhagic Shock/Reperfusion Injury’ PAUL F. STEMMER, M.D., LARISSA ROSARIO, M.D., SIN KIM, M.D., ANDRZEJ TARNAWSKI, M.D., AND I. JAMES SARFEH, M.D. Departments
of Surgery and Medicine (Gastroenterobgy), Long Beach Veterans Administration Medical Center, and the University of California, Irvine, California
Presented at the Annual Meeting of the Association for Academic Surgery, Louisville, Kentucky, November
E-18,1989
compared with normotensive controls [l-5]. Our observations have been confirmed by other investigators and have led to the current consensus that gastric mucosal changes in portal hypertension are indeed unique. The term “portal hypertensive gastropathy” has been introduced to distinguish this abnormality from the gastritis seen in non-PHT states [6, 71. The most frequent and serious complication of portal hypertension is hemorrhage from gastroesophageal varices and/or PHT gastropathy. Therefore, the response of PHT gastric mucosa to hemorrhagic shock needs to be examined. Since states of hypoperfusion predispose gastric mucosa to injury, and since PHT mucosa is already thus predisposed, then applying the hemorrhagic shock/ reperfusion (S/R) model to the study of PHT gastropathy assumes paramount clinical significance. The aim of this study is to determine whether S/R produces greater injury to the PHT gastric mucosa than to normotensive mucosa.
We have previously demonstrated that the portal hypertensive (PHT) gastric mucosa has unique functional and morphologic features which predispose it to increased damage by noxious agents such as aspirin or alcohol. In this study we examine the PHT gastric mucosa following hemorrhagic shock and reperfusion. Portal hypertension was produced in 12 rats using staged portal vein occlusion, and seven animals (controls) underwent sham procedures. All rats received 2 ml 0.1 N HCl intragastrically. Shock was then induced by withdrawing blood to reduce systemic arterial pressures to approximately 30 mm Hg for 20 min. Blood was then reinfused and stomachs were excised 20 min later for gross and microscopic quantitation of injury. We found that gross damage to gastric glandular mucosa was more than doubled in PHT rats over sham-operated controls. In PHT gastric mucosa, deep histologic necrosis involved 22.5 + 3.8% of mucosal section lengths compared with 6.9 + 2.0% in control mucosa (P < 0.005). Histologically, mucosal injury patterns were predominantly ischemic, with deep necrosis and disintegration of glands and microvessels, all prominently more extensive in PHT mucosa. We conclude that PHT gastric mucosa has significantly increased susceptibility to damage following hemorrhagic shock/reperfusion compared with portal normotensive mucosa. Since hemorrhagic shock is a frequent complication of portal hypertension, this study suggests clinical investigations of gastric mucosal function and pathophysiology in PHT patients following o isso Academic PMS. hc. hemorrhage and resuscitation.
MATERIALS
INTRODUCTION
Our previous clinical and experimental findings demonstrated that the portal hypertensive (PHT) gastric mucosa has characteristic functional and morphological features that increase its susceptibility to severe damage 1This work was supported by the Veterans Administration Research Service (VA Merit Review Award).
AND
METHODS
Male Sprague-Dawley rats (240-300 g) were used for all experiments. Portal hypertension was produced in 12 animals using a two staged procedure as previously described [2]. The animals underwent laparotomy while anesthetized with nembutal(50 mg/kg). The splenic vein was ligated at its juncture with the superior mesenteric vein. The portal vein was constricted with a 4-O silk ligature to the diameter of a PE 50 tubing. A second and heavier (2-O silk) ligature was loosely placed around the portal vein with a surgeon’s knot and the ends were exteriorized via the flanks and secured over the back. All animals received 3 ml isotonic saline intraperitoneally prior to closure. Sham-operated animals (n = 7) had their splenic and portal veins dissected only and without placement of ligatures. Animals were kept in individual metabolic cages with free access to rat chow and water. Three days after the original procedure in the experimental (PHT) animals, the ends of the external ligature were firmly pulled outward thereby completely occluding the portal vein. Sham-operated rats were handled in a similar
313 All
0022-4so4/90 $1.50 Copyright 0 1990 by Academic Press, Inc. rights of reproduction in any form reserved.
314
JOURNAL
OF SURGICAL
RESEARCH:
TABLE PP (mm Hg) Pre-S/R
VOL.
48, NO. 4, APRIL
1990
1
SAP (mm Hg) Post-S/R
Pre-S/R
% Mucosal injury
Post-S/R
Macroscopic
Histologic
PHT Sham
19 + 1 9+1
15 + 2 921
85 f 14 110 f 20
70 f 4 a7 f 7
7.8 k 1.3 3.1 f 0.5
22.5 f 3.8 6.9 f 2.0
P
OF SURGICAL
RESEARCH
48,313-318
(1990)
Portal Hypertension Predisposes the Gastric Mucosa to Hemorrhagic Shock/Reperfusion Injury’ PAUL F. STEMMER, M.D., LARISSA ROSARIO, M.D., SIN KIM, M.D., ANDRZEJ TARNAWSKI, M.D., AND I. JAMES SARFEH, M.D. Departments
of Surgery and Medicine (Gastroenterobgy), Long Beach Veterans Administration Medical Center, and the University of California, Irvine, California
Presented at the Annual Meeting of the Association for Academic Surgery, Louisville, Kentucky, November
E-18,1989
compared with normotensive controls [l-5]. Our observations have been confirmed by other investigators and have led to the current consensus that gastric mucosal changes in portal hypertension are indeed unique. The term “portal hypertensive gastropathy” has been introduced to distinguish this abnormality from the gastritis seen in non-PHT states [6, 71. The most frequent and serious complication of portal hypertension is hemorrhage from gastroesophageal varices and/or PHT gastropathy. Therefore, the response of PHT gastric mucosa to hemorrhagic shock needs to be examined. Since states of hypoperfusion predispose gastric mucosa to injury, and since PHT mucosa is already thus predisposed, then applying the hemorrhagic shock/ reperfusion (S/R) model to the study of PHT gastropathy assumes paramount clinical significance. The aim of this study is to determine whether S/R produces greater injury to the PHT gastric mucosa than to normotensive mucosa.
We have previously demonstrated that the portal hypertensive (PHT) gastric mucosa has unique functional and morphologic features which predispose it to increased damage by noxious agents such as aspirin or alcohol. In this study we examine the PHT gastric mucosa following hemorrhagic shock and reperfusion. Portal hypertension was produced in 12 rats using staged portal vein occlusion, and seven animals (controls) underwent sham procedures. All rats received 2 ml 0.1 N HCl intragastrically. Shock was then induced by withdrawing blood to reduce systemic arterial pressures to approximately 30 mm Hg for 20 min. Blood was then reinfused and stomachs were excised 20 min later for gross and microscopic quantitation of injury. We found that gross damage to gastric glandular mucosa was more than doubled in PHT rats over sham-operated controls. In PHT gastric mucosa, deep histologic necrosis involved 22.5 + 3.8% of mucosal section lengths compared with 6.9 + 2.0% in control mucosa (P < 0.005). Histologically, mucosal injury patterns were predominantly ischemic, with deep necrosis and disintegration of glands and microvessels, all prominently more extensive in PHT mucosa. We conclude that PHT gastric mucosa has significantly increased susceptibility to damage following hemorrhagic shock/reperfusion compared with portal normotensive mucosa. Since hemorrhagic shock is a frequent complication of portal hypertension, this study suggests clinical investigations of gastric mucosal function and pathophysiology in PHT patients following o isso Academic PMS. hc. hemorrhage and resuscitation.
MATERIALS
INTRODUCTION
Our previous clinical and experimental findings demonstrated that the portal hypertensive (PHT) gastric mucosa has characteristic functional and morphological features that increase its susceptibility to severe damage 1This work was supported by the Veterans Administration Research Service (VA Merit Review Award).
AND
METHODS
Male Sprague-Dawley rats (240-300 g) were used for all experiments. Portal hypertension was produced in 12 animals using a two staged procedure as previously described [2]. The animals underwent laparotomy while anesthetized with nembutal(50 mg/kg). The splenic vein was ligated at its juncture with the superior mesenteric vein. The portal vein was constricted with a 4-O silk ligature to the diameter of a PE 50 tubing. A second and heavier (2-O silk) ligature was loosely placed around the portal vein with a surgeon’s knot and the ends were exteriorized via the flanks and secured over the back. All animals received 3 ml isotonic saline intraperitoneally prior to closure. Sham-operated animals (n = 7) had their splenic and portal veins dissected only and without placement of ligatures. Animals were kept in individual metabolic cages with free access to rat chow and water. Three days after the original procedure in the experimental (PHT) animals, the ends of the external ligature were firmly pulled outward thereby completely occluding the portal vein. Sham-operated rats were handled in a similar
313 All
0022-4so4/90 $1.50 Copyright 0 1990 by Academic Press, Inc. rights of reproduction in any form reserved.
314
JOURNAL
OF SURGICAL
RESEARCH:
TABLE PP (mm Hg) Pre-S/R
VOL.
48, NO. 4, APRIL
1990
1
SAP (mm Hg) Post-S/R
Pre-S/R
% Mucosal injury
Post-S/R
Macroscopic
Histologic
PHT Sham
19 + 1 9+1
15 + 2 921
85 f 14 110 f 20
70 f 4 a7 f 7
7.8 k 1.3 3.1 f 0.5
22.5 f 3.8 6.9 f 2.0
P
